The Cb (breezula [clascoterone]) Community Thread

nick123

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What do you mean, how would that say something about whether upregulation is occurring?



Since it seems you looked through Cassiopea's documentation, did you per chance come across the papers for the phase I and II Breezula studies? I've tried looking for those, but been unable to find them. Only a paper briefly summarizing both.



Well, loss of effectiveness is what we are seeing, the question is what is the mechanism if not upregulation.

If TAHW decreased at the same rate as TAHC, then we can conclude that miniaturisation was occuring at an accelerated rate. The TAHC drop off could potentially just be vellus hairs that grew between 1-6 month but Breezula was not enough to maintain in long term. AFAIK the previous studies were not 12 months long, so they'd be useless. Just like the Phase 3 will be as that's only going to be 6 months long.
 

nick123

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I'm not even convinced of AR upregulation from AR antagonists like CB. It's just one theory for what's happening from CB. Another is some type of negative feedback on estrogen receptor expression. I think AR upregulation is more likely from AR antagonists, and I don't see any reason to believe it happens with 5-ARIs.
@pegasus2

My only argument/confusion about AR upregulation is the 2.5% dosage between the 6 and 12 months. Between months 6-9 there was a TAHC decrease of 10.3 but between months 9-12 there was only a TAHC decrease of 2.2. I'm wondering if this is how AR upregulation would behave?

My thinking (probably naive and optimistic) for a potential reason for the post 6 month drop off could be Breezula caused lots of vellus (non-terminal) hairs to sprout but Breezula couldn't maintain these hairs long term? This is why I wanted the 12 month TAHW results vs Baseline because if they followed the same pattern then we can say miniaturisation was occurring at a faster rate than placebo and for sure AR upregulation is occurring?

I'm also confused about, why 6 months exactly? What's going on in the DP that would say if the receptors are being continually deprived of androgens for exactly 6 months, then they will upregulate? Why wouldn't it start happening immediately? Or does it start happening immediately but just takes 6 months to upregulate the androgen receptors?

1612960687457.png
 
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FilthyFrancis

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Assuming that's accurate, a lack of AR upregulation in the sebaceous gland doesn't prove a lack of AR upregulation in the DP anymore than AR upregulation in the prostate proves AR upregulation in the DP. You're comparing apples to oranges, which is fine for forming a hypothesis, but it doesn't prove anything.

While I agree with @pegasus2 on the fact that AR upregulation in scalp tissue has never been proven and can only be hypothesized at this stage, I don't find this hypothesis too far-fetched given that AR upregulation (even with finasteride) is a well-documented phenomenon in prostate tissue already. If it happens down there, why not up in the scalp.

______________________________

https://pubmed.ncbi.nlm.nih.gov/21557276/

Finasteride upregulates expression of androgen receptor in hyperplastic prostate and LNCaP cells: implications for chemoprevention of prostate cancer​

"In our study, finasteride influenced AR expression in benign prostate tissue and prostate cancer cell."

https://pubmed.ncbi.nlm.nih.gov/20155615/

Lycopene effects contributing to prostate health​

"During disease progression, and after androgen ablation therapy, the remaining operational pathways are upregulated to compensate for the lost growth signal, finally resulting in androgen-independent prostate cancer"

_____________________________

I had a terrible finasteride course (very unusual acne, oily and super itchy scalp, intense shedding and hastened miniaturization) but can't say for sure it was related to upregulation.

I find it hard to believe one could have acute AR upregulation while others would see upregulation rising overtime.
 

trialAcc

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While I agree with @pegasus2 on the fact that AR upregulation in scalp tissue has never been proven and can only be hypothesized at this stage, I don't find this hypothesis too far-fetched given that AR upregulation (even with finasteride) is a well-documented phenomenon in prostate tissue already. If it happens down there, why not up in the scalp.

______________________________

https://pubmed.ncbi.nlm.nih.gov/21557276/

Finasteride upregulates expression of androgen receptor in hyperplastic prostate and LNCaP cells: implications for chemoprevention of prostate cancer​

"In our study, finasteride influenced AR expression in benign prostate tissue and prostate cancer cell."

https://pubmed.ncbi.nlm.nih.gov/20155615/

Lycopene effects contributing to prostate health​

"During disease progression, and after androgen ablation therapy, the remaining operational pathways are upregulated to compensate for the lost growth signal, finally resulting in androgen-independent prostate cancer"

_____________________________

I had a terrible finasteride course (very unusual acne, oily and super itchy scalp, intense shedding and hastened miniaturization) but can't say for sure it was related to upregulation.

I find it hard to believe one could have acute AR upregulation while others would see upregulation rising overtime.
Sounds like what I'm experiencing on finasteride. My only issue is that I was already on it for years and this was triggered by restarting it after a short break. Quitting for me is giving up on that 6 years of maintenance, even though i've lost much of it already the last 4~ months. Tough call for me to stay on it or quit.
 

FilthyFrancis

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Sounds like what I'm experiencing on finasteride. My only issue is that I was already on it for years and this was triggered by restarting it after a short break. Quitting for me is giving up on that 6 years of maintenance, even though i've lost much of it already the last 4~ months. Tough call for me to stay on it or quit.
Let's not hijack this thread.

I can't tell you much more than that I regret not staying on finasteride longer. I wish I had pursued until the 1-year mark just for the sake of being able to reject the idea of taking 5ARI's again if ineffective.
 

Dimitri001

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@pegasus2

My only argument/confusion about AR upregulation is the 2.5% dosage between the 6 and 12 months. Between months 6-9 there was a TAHC decrease of 10.3 but between months 9-12 there was only a TAHC decrease of 2.2. I'm wondering if this is how AR upregulation would behave?

My thinking (probably naive and optimistic) for a potential reason for the post 6 month drop off could be Breezula caused lots of vellus (non-terminal) hairs to sprout but Breezula couldn't maintain these hairs long term? This is why I wanted the 12 month TAHW results vs Baseline because if they followed the same pattern then we can say miniaturisation was occurring at a faster rate than placebo and for sure AR upregulation is occurring?

I'm also confused about, why 6 months exactly? What's going on in the DP that would say if the receptors are being continually deprived of androgens for exactly 6 months, then they will upregulate? Why wouldn't it start happening immediately? Or does it start happening immediately but just takes 6 months to upregulate the androgen receptors?

View attachment 156778
Keep in mind, we don't know that THAC starts falling after exactly 6 months. We only get a snapshot of it at 3, 6 and 9 months. It's possible it peaked at 4 and started coming down then and at month 6 we get a snapshot of it falling, but not yet below the 3 month mark.

It's also possible it continues rising after 6 to peak at 8 months and then falls off a cliff in a month.
 

tgfbeta

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Hey @tgfbeta, how is it going with your sides?
Not so good. Long story short, I developed penile fibrosis which was found with an ultrasound test. I'm currently taking cialis daily and undergoing weekly shockwave therapy to help break up the fibrotic tissue that's causing erectile dysfunction. All of my symptoms are in line with pfs, except for cognitive/mental sides. I don't think it ever crossed the blood-brain barrier, which I'm very grateful for. Otherwise this would have been life-altering.

I'm no longer taking clomid + anastrozole, which were supposed to increase my hormone levels. My total testosterone shot up to 1200 ng/dl, and my DHT to 85 ng/dl. I stopped taking them because I didn't feel any benefit to my situation, besides massive scalp inflammation caused by the excessive DHT. The urologist that prescribed me these medications did not perform an ultrasound, so the root cause was not being addressed.

I'm in the middle of midterms at school so I haven't been able to get the CB tested. I will once I have more time, but it hasn't been my priority. Going through this experience has shown me the flip side to messing with androgen receptors. I personally do not think that CB is safe, because some of it will go systemic and reach the cells in penile tissue. In my case, the doctor believes that CB went systemic, blocking AR in the penis and triggering cellular apoptosis. Moreover, the "dead" tissue was replaced with inelastic fibrous tissue, which restricts blood flow and erection quality. I will not be trying Winlevi, Breezula, or any anti-androgen in the future, due to my experience.

This thread seems a little dead, but I'm curious if any of the original posters came across side effects like mine. I do not suspect that I'm the only person. Cheers everybody.
 

trialAcc

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Not so good. Long story short, I developed penile fibrosis which was found with an ultrasound test. I'm currently taking cialis daily and undergoing weekly shockwave therapy to help break up the fibrotic tissue that's causing erectile dysfunction. All of my symptoms are in line with pfs, except for cognitive/mental sides. I don't think it ever crossed the blood-brain barrier, which I'm very grateful for. Otherwise this would have been life-altering.

I'm no longer taking clomid + anastrozole, which were supposed to increase my hormone levels. My total testosterone shot up to 1200 ng/dl, and my DHT to 85 ng/dl. I stopped taking them because I didn't feel any benefit to my situation, besides massive scalp inflammation caused by the excessive DHT. The urologist that prescribed me these medications did not perform an ultrasound, so the root cause was not being addressed.

I'm in the middle of midterms at school so I haven't been able to get the CB tested. I will once I have more time, but it hasn't been my priority. Going through this experience has shown me the flip side to messing with androgen receptors. I personally do not think that CB is safe, because some of it will go systemic and reach the cells in penile tissue. In my case, the doctor believes that CB went systemic, blocking AR in the penis and triggering cellular apoptosis. Moreover, the "dead" tissue was replaced with inelastic fibrous tissue, which restricts blood flow and erection quality. I will not be trying Winlevi, Breezula, or any anti-androgen in the future, due to my experience.

This thread seems a little dead, but I'm curious if any of the original posters came across side effects like mine. I do not suspect that I'm the only person. Cheers everybody.
I wish you the best but you need to get that CB tested before making these types of claims, man. Teenagers are about to be using this stuff for months on end to fight acne and I legitimately cannot see how there is even a remote possibility that some of them are about to get penile fibrosis after literally 7+ FDA approved studies (between acne and hairloss) found nothing similar.
 

tgfbeta

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I wish you the best but you need to get that CB tested before making these types of claims, man. Teenagers are about to be using this stuff for months on end to fight acne and I legitimately cannot see how there is even a remote possibility that some of them are about to get penile fibrosis after literally 7+ FDA approved studies (between acne and hairloss) found nothing similar.
You're not wrong, but I'm just sharing my personal experience with the supposed drug. This is all contingent on me having used the legit chemical, which is why I haven't attempted to claim that CB is dangerous. However, I do trust my current urologist who is treating me. Independent of what happened to me, he does not believe that CB is free from systemic effects. To the contrary, he thinks the HPA-axis suppression is potentially catastrophic. But that's just one doctor's opinion. Thanks for the wishes.
 

mooreu

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You're not wrong, but I'm just sharing my personal experience with the supposed drug. This is all contingent on me having used the legit chemical, which is why I haven't attempted to claim that CB is dangerous. However, I do trust my current urologist who is treating me. Independent of what happened to me, he does not believe that CB is free from systemic effects. To the contrary, he thinks the HPA-axis suppression is potentially catastrophic. But that's just one doctor's opinion. Thanks for the wishes.

Can you say where you obtained your CB from?
 

mooreu

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science.bio

I have no personal experience with them so I can't really judge. You might want to have it tested to be sure it was CB and not a different substance. And if Mustang's test of Kane's CB is any indication then your CB was far from pure.
 

Keratinpro

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I have no personal experience with them so I can't really judge. You might want to have it tested to be sure it was CB and not a different substance. And if Mustang's test of Kane's CB is any indication then your CB was far from pure.
Did Mustang's test show that Kane's CB was impure? I personally wouldn't put a drug in my system from some 3rd Party website. I'm sure if CB had this type of adverse reaction, they would state it in their trials as well as it being not FDA approved because it's aimed at teenagers as well as women. Cassiopea stated that they had no serious adverse reactions, I feel once the drug comes out and people try it we will have a better gauge on whether it produces systemic side effects or not.
 
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